Discovery of trait markers for psychiatric disorders is an urgently sought but elusive goal. Trait markers with acceptable levels of sensitivity and specificity would not only facilitate differential diagnosis and choice of suitable treatment, but would help illuminate etiological factors and promote programs of primary prevention. There are currently no validated "trait" markers for depression. A promising area of inquiry is the tyramine test. Sandler et al. 1 reported that patients with endogenous unipolar depression excrete significantly lower amounts of urinary sulfate conjugated tyramine in response to an oral tyramine load than normals and that this apparent conjugation deficit persists after recovery from depression, suggesting a "trait" marker. Ghose and Coppen 2 observed an enhanced pressor response to intravenous tyramine in depressives. Their data suggest that the increased tyramine sensitivity persisted after recovery from depression (another trait marker?). Patient with depression will be re- challenged with oral tyramine during depression, while taking conventional antidepressants and after recovery to determine state independent, persistence of the deficit and the effect of medication on the reproducibility of the test. Normals will be re-tested at similar time intervals as controls. We hypothesize that the most likely mechanisms for the reduced tyramine sulfate excretion are an increase in monoamine oxidase or a defect in sulfate conjugation. We intend to test this in depressives and normal controls by: (1) measurement of platelet monoamine oxidase and phenolsulfotransferase activity; (2) determination of the pharmacokinetic profiles of tyramine-o-sulfate in plasma and urine. We also propose to determine whether there is any correlation between the apparent tyramine sulfate conjugation defect and enhanced intravenous tyramine dose-pressor response as putative trait markers by conducting both of these tests in the same subjects.